Evaluación in vitro de los agentes neurotóxicos liberados por las células de la microglía, infectadas con el virus dengue neuroadaptado (D4MB-6)
dc.contributor.advisor | Velandia-Romero, Myriam Lucía | |
dc.contributor.advisor | Castellanos, Jaime | |
dc.contributor.author | Beltrán Zúñiga, Edgar Orlando | |
dc.contributor.orcid | Castellanos, Jaime [0000-0003-1596-8383] | |
dc.contributor.orcid | Velandia-Romero, Myriam Lucía [0000-0002-3340-7304] | |
dc.date.accessioned | 2021-02-22T21:21:43Z | |
dc.date.available | 2021-02-22T21:21:43Z | |
dc.date.issued | 2021 | |
dc.description.abstract | La infección causada por el virus del dengue (DENV) se ha relacionado con el desarrollo de alteraciones neurológicas y comportamentales en humanos. Dicha asociacione se ha confirmado por el desarrollo de signos claros de alteración neurológica durante y después de la infección y por la presencia de proteínas y/o RNA viral en líquido cefaloraquídeo o en muestras de tejido nervioso obtenidas post morten. Esto sugiere que el virus puede invadir el Sistema Nervioso Central (SNC). Por la dificultad de reproducir los signos y síntomas del dengue en animales, nuestro grupo desarrolló un modelo in vivo de neuroinfección en el cual ratones neonatos se inocularon a nivel periférico con una cepa de virus adaptada a tejido nervioso (D4MB-6). Como resultado, se observó que la variante viral logró invadir el SNC e infectó algunas poblaciones celulares como neuronas, oligodendrocitos y células de la microglía. Estas últimas presentaron evidentes cambios morfológicos que sugerían activación. Adicionalmente se observó que en el tejido nervioso de animales infectados la infección indujo una exacerbada respuesta inmune y la excitotoxicidad por glutamato, espectos que en conjunto causaron la muerte neuronal y el daño en la arquitectura tisular. Sin embargo, la población celular del tejido nervioso que secreta estas moléculas no ha sido identificada aún. Experimentalmente se ha demostrado que en diferentes patologías -incluso virales- la principal fuente de citoquinas pro-inflamatorias, glutamato y otros agentes provienen de las células de la microglía infectadas y/o activadas. Todos los agentes producidos y liberados por estas células, pueden de manera conjunta o independiente ocasionar el daño y la muerte neuronal. Por lo tanto, en este trabajo se evaluó en un cultivo primario de células de la microglía de ratón lactante, su susceptibilidad a la infección con la variante adaptada -D4MB-6- o no a tejido nervioso y algunos aspectos relacionados con su activación. Como resultado se observó que las células microgliales presentaron una alta susceptibilidad a la infección y en los tiempos post-infección evaluados presentaron altas tasas de proliferación y supervivencia. Adicionalmente se observó que las células presentaron cambios morfológicos y produjeron algunas moléculas pro-inflamatorias y glutamato, que indujeron a las células a sostener en los tiempos evaluados un estado de activación que fue modulado y regulado por los fármacos VPA o MK-801. En conjunto estos resultados permitieron describir que la infección por DENV indujo la activación y producción de agentes pro-inflamatorios y glutamato por parte de las células de la microglía, por lo tanto, sugerimos que estas células son centrales en el desarrollo de la nueuroinfección y neuropatogenia causada por el DENV. | spa |
dc.description.degreelevel | Maestría | spa |
dc.description.degreename | Magíster en Ciencias Básicas Biomédicas | spa |
dc.format.mimetype | application/pdf | |
dc.identifier.instname | instname:Universidad El Bosque | spa |
dc.identifier.reponame | reponame:Repositorio Institucional Universidad El Bosque | spa |
dc.identifier.repourl | repourl:https://repositorio.unbosque.edu.co | |
dc.identifier.uri | https://hdl.handle.net/20.500.12495/5409 | |
dc.publisher.faculty | Facultad de Medicina | spa |
dc.publisher.grantor | Universidad El Bosque | spa |
dc.publisher.program | Maestría en Ciencias Básicas Biomédicas | spa |
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dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | * |
dc.rights.accessrights | info:eu-repo/semantics/openAccess | |
dc.rights.accessrights | https://purl.org/coar/access_right/c_abf2 | |
dc.rights.creativecommons | 2016 | |
dc.rights.local | Acceso abierto | spa |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | Células de la microglía | spa |
dc.subject | Neuropatogenia | spa |
dc.subject | DENV | spa |
dc.subject | Virus neuroadapatado | spa |
dc.subject | Activación celular | spa |
dc.subject.decs | Neurotoxinas | spa |
dc.subject.decs | Técnicas in vitro | spa |
dc.subject.decs | Virus del dengue | spa |
dc.subject.nlm | W 50 | |
dc.title | Evaluación in vitro de los agentes neurotóxicos liberados por las células de la microglía, infectadas con el virus dengue neuroadaptado (D4MB-6) | spa |
dc.title.translated | In vitro assessment of the neurotoxic agents produced by infected microglial cells by a neuroadapted strain of Dengue Virus-D4MB-6 | spa |
dc.type.coar | https://purl.org/coar/resource_type/c_bdcc | |
dc.type.coarversion | https://purl.org/coar/version/c_970fb48d4fbd8a85 | |
dc.type.driver | info:eu-repo/semantics/masterThesis | |
dc.type.hasversion | info:eu-repo/semantics/acceptedVersion | |
dc.type.local | Tesis/Trabajo de grado - Monografía - Maestría | spa |
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